Project Abstract Whereas current meniscal tissue-engineering approaches largely model the tissue using small strain approximations, this supplement aims to design tissue-engineered neomenisci based on optimization of hyperelastic parameters. Hyperelasticity accounts for the mechanical behavior of elastic materials at large or finite deformations, hereby defined as greater than 10% strain. This degree of deformation is commonly observed in physiological environments. For example, the medial posterior horn has been reported to undergo 40% strain under normal loading conditions, well beyond the threshold for small strain approximations. In this proposal, we will use computational and experimental methods to investigate tissue-engineered meniscus performance under large deformations, a key metric to assess translatability. We will examine several mechanical models to develop a quantitative and physiologically relevant characterization profile for native meniscus fibrocartilage (Aim 1). We will then optimize a regimen of exogenous stimuli and evaluate their effect on hyperelastic parameters, with particular interest in anisotropic changes (Aim 2). These parameters are central to establishing our design criteria for engineered neomenisci. Together, these aims represent an exceedingly novel approach to tissue-engineering and will drive the development of a mechanically robust meniscus regenerative treatment option.